Broadly conceived, my research objectives are to understand the relationship between the internal environment and behavior. Changes in the milieu interieur of an animal evoke certain behaviors (e.g., increases in blood osmotic pressure are followed by antidiuresis and drinking of water), behaviors which are regulatory in that they accomplish a return to a more or less homeostatic condition. The neural mechanisms which sense changes in the blood or other body fluids are of specific interest to me. Such internal sensing systems must be capable of tranducing physicochemical fluctuations into some kind of cellular response, be it electrical, hormonal or both. The output of these internal "sense organs" must then be integrated into directed behavior, appropriate to the prevailing circumstances. It is, however, the detectors of the imbalance which initiate the chain of events, and about which we know so little. Our recent work on the nucleus circularis of the rat has led us to postulate it as a putative osmoreceptor. The work proposed here will verify its role and investigate the relationships of other hypothalamic systems in the regulatory process. Various anatomical and physiological techniques will be used in our investigations, including extra- and intracellular recording, retrograde and anterograde transport techniques, autoradiography, nucleolar counts, electron microscopy and measurements of blood constituents such as hormones, ions, and osmotic pressure.